The Dental Biology Unit is directed by Dr. Songtao Shi and currently includes Drs. Masako Miura, Byoung-Moo Seo, Wataru Sonoyama, Yasuo Miura and Carolyn Coppe. Our research is focused on isolation and characterization of dental/craniofacial associated stem cells including stem cells derived from Dental Pulp, periodontal ligament and bone marrow stromal. Postnatal bone marrow stromal stem cells (BMSSCs) and dental pulp stem cells (DPSCs) are multipotent stem cells, capable of differentiating into various cell types including, but not limited to, osteoblasts/odontoblasts, adipocytes, and neural cells. Previous studies also demonstrated that BMSSCs were able to differentiate into chondrocytes and muscle cells. Upon in vivo transplantation, BMSSCs and DPSCs consistently differentiate into functional osteo/dontoblasts to generate a bone/marrow organ structure and a dentin/pulp complex, respectively. However, the detailed mechanisms involved in the initiation and maintenance of the bone/marrow organ and dentin/pulp complex have yet to be determined. We revealed that BMSSCs and DPSCs share a similar timing for forming mineralized tissue, leading to the establishment of a bone/marrow organ for BMSSCs and a dentin/pulp complex for DPSCs. Elevated expression of basic fibroblast growth factor (bFGF) and matrix metalloproteinase 9 (MMP-9, gelatinase B) was found to be associated with the formation of hematopoietic marrow in BMSSC transplants, but not in the connective tissue of DPSC transplants. The expression of dentin sialoprotein (DSP) specifically marked dentin synthesis in DPSC transplants. Moreover, DPSCs were found to be able to generate reparative dentin-like tissue on the surface of human dentin in vivo. Our study provided direct evidence to suggest that osteogenesis and dentinogenesis mediated by BMSSCs and DPSCs, respectively, may be regulated by distinct mechanisms, leading to the different organization of the mineralized and non-mineralized tissues. Periodontal diseases are one of the most common bacterial infections leading to the destruction of periodontal tissues including periodontal ligament (PDL), cementum, and bone. They are the major cause of tooth loss in adults and post a significant public health burden worldwide. Periodontal ligament (PDL) is a specialized connective tissue that connects cementum and alveolar bone to maintain teeth in situ, support teeth for function, and preserve tissue homeostasis. We tested the notion that human PDL contains stem cells that may be utilized for periodontal tissue regeneration. We demonstrated for the first time that PDL stem Cells (PDLSCs) subsisted within PDL tissue compartment and they expressed the mesenchymal stem cell markers, STRO-1 and CD146/MUC18. Under defined culture conditions, PDLSCs were able to differentiate into cementoblast-like cells, adipocytes, and collagen-forming cells in vitro. PDLSCs also exhibited the capacity to generate a cementum/PDL-like structure and contribute to periodontal tissue repair in vivo, when transplanted into immunocompromised rodents. PDLSCs have potentials to generate cementum/PDL-like tissue in vivo. Importantly, human PDLSCs can be obtained from an easily accessible tissue resource and expanded ex vivo for therapeutic purposes. PDLSC-mediated tissue regeneration may provide a promising therapy for the reconstruction of tooth supporting tissues destroyed by periodontal diseases.